Process for the synthesis of diaminopyridines from glutaronitriles

ABSTRACT

A liquid-phase process is provided for the manufacture from glutaronitriles and related compounds of 2,6-diaminopyridine and related compounds, which are used industrially as compounds and as components in the synthesis of a variety of useful materials. The synthesis proceeds by means of a dehydrogenative aromatization process.

This application claims the benefit of U.S. Provisional Application No.60/876,577, filed 21 Dec. 2006, which is incorporated in its entirety asa part hereof for all purposes.

TECHNICAL FIELD

This invention relates to the manufacture of 2,6-diaminopyridine andrelated compounds, which are used industrially as compounds and ascomponents in the synthesis of a variety of useful materials.

BACKGROUND

The compound 2,6-diaminopyridine (“DAP”), which is shown by thestructural formula below

is a useful starting material for preparing monomers for rigid rodpolymers such as described in WO 94/25506, as well as for dyes, metalligands, medicines and pesticides.

It is well-known to prepare DAP by means of the Chichibabin aminationreaction in which pyridine is reacted with sodium amide in an organicsolvent. This is a complicated reaction requiring relatively severeconditions (e.g. 200° C. at elevated pressure). Additionally, handlingsodium amide and isolating the desired product from this complex mixtureare difficult operations to perform on a commercial scale.

Pyridine derivatives have also been synthesized through the conversionof acylic dinitriles (see, for example, GB 2,165,844; and U.S. Pat. Nos.5,066,809; 4,876,348; 6,118,003; 4,603,207; 5,028,713; and 4,051,140).There are several examples of this type of transformation in the vaporphase and, to a lesser extent, in the liquid phase. For example, U.S.Pat. No. 4,876,348 teaches the ammoxidation of 2-methylglutaronitrile to3-cyanopyridine. The two-step process involves the conversion of2-methylglutaronitrile to a mixture of 3-methylpyridine and3-methylpiperidine, followed by the vapor phase ammoxidation of thismixture with NH₃ and O₂ in the presence of a complex metal oxide to givethe product 3-cyanopyridine.

A need thus remains for a process wherein, on an industrial scale, itwould be possible to form pyridine derivatives in the liquid phase inthe presence of a heterogeneous catalyst, which would facilitateseparating and recycling the catalyst.

SUMMARY

The inventions disclosed herein include processes for the preparation ofdiaminopyridines and related compounds, processes for the preparation ofproducts into which diaminopyridines and related compounds can beconverted, and the products obtained and obtainable by such processes.

One embodiment of this invention involves a process for the synthesis ofa compound as described by the structure of Formula (I)

by contacting a compound as described by the structure of Formula (II)

with a chemical oxidant and/or a dehydrogenation catalyst in liquidammonia neat, or in a mixture of liquid ammonia and a polar, aproticsolvent, to form a reaction mixture; and heating the reaction mixture toproduce a Formula (I) compound;

wherein R¹ and R² are each independently selected from (a) H; (b) ahydrocarbyl group; (c) NR³R⁴ wherein R³ and R⁴ are each independentlyselected from H and a hydrocarbyl group;

wherein R⁵ is a hydrocarbyl group; and (e) YR⁶ wherein Y is selectedfrom O and S and R⁶ is selected from H, a hydrocarbyl group, and

wherein R⁵ is a hydrocarbyl group.

A further embodiment of the processes hereof involves a process forpreparing a Formula (I) compound that further includes a step ofsubjecting the Formula (I) compound to a reaction (including amulti-step reaction) to prepare therefrom a compound, monomer, oligomeror polymer.

In yet another embodiment of this invention, a new compound as describedby the structure of Formula (III) is provided:

DETAILED DESCRIPTION

In a process as described herein, compounds of Formula (I) are preparedfrom glutaronitrile and related compounds by means of a dehydrogenativearomatization process in the presence of a chemical oxidant and/or adehydrogenation catalyst.

In one embodiment of the processes hereof, a compound of Formula (I) issynthesized from an acylic dinitrile compound of Formula (II) bycontacting the acylic dinitrile compound with a chemical oxidant and/ora dehydrogenation catalyst in liquid ammonia neat or in a mixture ofammonia and a polar, aprotic solvent to form a reaction mixture, andheating the reaction mixture to produce the Formula (I) product.

In Formulas (I) and (II), R¹ and R² are each independently selected from(a) H; (b) a hydrocarbyl group; (c) NR³R⁴ wherein R³ and R⁴ are eachindependently selected from H and a hydrocarbyl group;

wherein R⁵ is a hydrocarbyl group; and (e) YR⁶ wherein Y is selectedfrom O and S and R⁶ is selected from H, a hydrocarbyl group, and

wherein R⁵ is a hydrocarbyl group.

Examples of hydrocarbyl groups suitable for use in R² to R⁵ includewithout limitation

a C₁˜C₁₈, or C₁˜C₁₀, straight-chain or branched, saturated orunsaturated, substituted or unsubstituted, hydrocarbyl radical;

a C₃˜C₁₂ cyclic aliphatic, saturated or unsaturated, substituted orunsubstituted, hydrocarbyl radical; or

a C₆˜C₁₂ aromatic substituted or unsubstituted hydrocarbyl radical.

In various embodiments, any one or more of R² to R⁵ may be a methyl,ethyl, propyl, butyl, pentyl, hexyl or phenyl radical. In a substitutedhydrocarbyl radical, one or more O or S atoms may optionally besubstituted for any one or more of the in-chain or in-ring carbon atoms,provided that the resulting structure contains no —O—O— or —S—S—moieties, and provided that no carbon atom is bonded to more than oneheteroatom.

Preferably, one or both of R¹ and R² is H. When R¹ and R² are both H,the acylic dinitrile is glutaronitrile (“GN”) and the compound ofFormula (I) is 2,6-diaminopyridine (“DAP”), as shown below:

One or both of R¹ and R² may be NH₂. When R¹ and R² are both NH₂, thecompound of Formula (II) is 2,4-diaminopentanedinitrile, and thecompound of Formula (I) is 2,3,5,6-tetraminopyridine (“TAP”) whichitself is a useful industrial intermediate.

When the compound of Formula (II) is2,4-bis(dimethylamino)pentanedinitrile [i.e. R¹ and R² are bothN(CH₃)₂], a new compoundN³,N³,N⁵,N⁵-tetramethylpyridine-2,3,5,6-tetraamine, as shown by thestructure of Formula (III), is produced:

Various compounds of Formula (II), as used in the processes hereof, maybe synthesized by processes known in the art, or are availablecommercially from suppliers such as Alfa Aesar (Ward Hill, Mass.), CityChemical (West Haven, Conn.), Fisher Scientific (Fairlawn, N.J.),Sigma-Aldrich (St. Louis, Mo.) or Stanford Materials (Aliso Viejo,Calif.).

In a process hereof, a compound of Formula (II) is contacted with achemical oxidant and/or a dehydrogenation catalyst. Thus, a chemicaloxidant and a dehydrogenation catalyst may each be used with or without(i.e. in the absence of) the other.

Chemical oxidants suitable for use herein include without limitationsulfur, sulfur dioxide, oxygen, selenium,2,3-dichloro-5,6-dicyano-p-benzoquinone (“DDQ”),2,3,5,6-tetrachloro-p-benzoquinone (“chloranil”), aluminum chloride,arsenic oxide, manganese dioxide, potassium ferricyanide, nitrobenzene,chlorine, bromine, iodine, and the like.

A dehydrogenation catalyst as used herein may be a homogeneous catalystor a heterogeneous catalyst. A dehydrogenation catalyst suitable for useherein typically contains at least one metal or metal salt wherein themetal or metal salt is selected, for example, from elements of GroupsIVA, VA, VIA, VIIA, VIII, IB, and IIB, and salts of said elements [assuch groups are described in the periodic table in a reference such asAdvanced Inorganic Chemistry by Cotton and Wilkinson, Interscience NewYork, 2nd Ed. (1966)]. A particular metal or metal salt may be selectedfrom Group VIII elements and salts of said elements (e.g. iron, cobaltand nickel), and/or the platinum group metals including ruthenium,rhodium, palladium, osmium, iridium and platinum. The platinum groupmetals and their salts are preferred, more preferably platinum andpalladium and their salts. Sponge metal catalysts may also be effective,including without limitation Raney iron, Raney nickel and Raney cobalt.Raney nickel is preferred.

In a heterogeneous catalyst, a metal or metal salt may be deposited uponany suitable support with a sufficiently high surface area. The supportmay be amorphous or may possess a crystalline structure or contain bothamorphous and crystalline portions. The support may be a solid metaloxide or solid non-metal oxide, each with surface —OH groups. Examplesof such metal oxides are those from tri- and tetravalent metals, whichmay be a transition or non-transition metal or any rare earth such asalumina, titania, cobaltic oxide, zirconia, ceria, molybdenum oxide andtungsten oxide. An example of a typical non-metal oxide is silica. Thesupport may also be a zeolite or zeotype material having a structuremade up of tetrahedra joined together through oxygen atoms to produce anextended network with channels of molecular dimensions. Thezeolite/zeotype materials have SiOH and/or AlOH groups on the externalor internal surfaces. The support may also be activated carbon, coke orcharcoal. Preferably, the support is at least one of alumina, silica,silicalite, ceria, titania, or carbon, more preferably alumina, silicaor carbon.

The liquid ammonia, whether used neat or in a solvent, is typically usedin an amount of from about 1 to about 100 moles per mole of compound ofFormula (II). When a polar, aprotic solvent is used, examples ofsuitable solvents include without limitation 1,4-dioxane,tetrahydrofuran, acetone, acetonitrile, dimethylformamide, and pyridine.Mixed solvents can be used, such as 1,4-dioxane plus pyridine, but usingammonia neat is preferred (the term “neat” referring to the absence ofsolvent).

The reaction may be run at a temperature that is typically in the rangeof about 200° C. to about 300° C. Reaction time is typically about 3 toabout 45 hours. The reaction is preferably run in a closed vessel.

A compound of Formula (I) or (III) (a “Pyridine Product”) may, asdesired, be isolated and recovered. The Pyridine Product may also,however, be subjected with or without recovery from the reaction mixtureto further steps to convert it to another product such as anothercompound (e.g. a monomer), or an oligomer or a polymer. Anotherembodiment of a process hereof thus provides a process for converting aPyridine Product, through a reaction (including a multi-step reaction),into another compound, or into an oligomer or a polymer. A PyridineProduct may be made by a process such as described above, and thenconverted, for example, by being subjected to a polymerization reactionto prepare an oligomer or polymer therefrom, such as those having amidefunctionality, imide functionality, or urea functionality, or apyridobisimidazole-2,6-diyl(2,5-dihydroxy-p-phenylene) polymer.

A Pyridine Product such as a diaminopyridine may be converted into apolyamide oligomer or polymer by reaction with a diacid (or diacidhalide) in a process in which, for example, the polymerization takesplace in solution in an organic compound that is liquid under theconditions of the reaction, is a solvent for both the diacid(halide) andthe diaminopyridine, and has a swelling or partial salvation action onthe polymeric product. The reaction may be effected at moderatetemperatures, e.g. under 100° C., and is preferably effected in thepresence of an acid acceptor that is also soluble in the chosen solvent.Suitable solvents include methyl ethyl ketone, acetonitrile,N,N-dimethylacetamide dimethyl formamide containing 5% lithium chloride,and N-methylpyrrolidone containing a quaternary ammonium chloride suchas methyl tri-n-butyl ammonium chloride or methyl-tri-n-propyl ammoniumchloride. Combination of the reactant components causes generation ofconsiderable heat and the agitation, also, results in generation of heatenergy. For that reason, the solvent system and other materials arecooled at all times during the process when cooling is necessary tomaintain the desired temperature. Processes similar to the foregoing aredescribed in U.S. Pat. Nos. 3,554,966; 4,737,571; and CA 2,355,316.

A Pyridine Product such as a diaminopyridine may also be converted intoa polyamide oligomer or polymer by reaction with a diacid (or diacidhalide) in a process in which, for example, a solution of thediaminopyridine in a solvent may be contacted in the presence of an acidacceptor with a solution of a diacid or diacid halide, such as a diacidchloride, in a second solvent that is immiscible with the first toeffect polymerization at the interface of the two phases. Thediaminopyridine may, for example, be dissolved or dispersed in a watercontaining base with the base being used in sufficient quantities toneutralize the acid generated during polymerization. Sodium hydroxidemay be used as the acid acceptor. Preferred solvents for thediacid(halide) are tetrachloroethylene, methylenechloride, naphtha andchloroform. The solvent for the diacid(halide) should be a relativenon-solvent for the amide reaction product, and be relatively immisciblein the amine solvent. A preferred threshold of immiscibility is asfollows: an organic solvent should be soluble in the amine solvent notmore than between 0.01 weight percent and 1.0 weight percent. Thediaminopyridine, base and water are added together and vigorouslystirred. High shearing action of the stirrer is important. The solutionof acid chloride is added to the aqueous slurry. Contacting is generallycarried out at from 0° C. to 60° C., for example, for from about 1second to 10 minutes, and preferably from 5 seconds to 5 minutes at roomtemperature. Polymerization occurs rapidly. Processes similar to theforegoing are described in U.S. Pats. No. 3,554,966 and 5,693,227.

A Pyridine Product such as a diaminopyridine may also be converted intoa polyimide oligomer or polymer by reaction with a tetraacid (or halidederivative thereof) or a dianhydride in a process in which each reagent(typically in equimolar amounts) is dissolved in a common solvent, andthe mixture is heated to a temperature in the range of 100˜250° C. untilthe product has a viscosity in the range of 0.1˜2 dL/g. Suitable acidsor anhydrides include benzhydrol 3,3′,4,4′-tetracarboxylic acid,1,4-bis(2,3-dicarboxyphenoxy)benzene dianhydride, and3,3′,4,4′-benzophenone tetracarboxylic acid dianhydride. Suitablesolvents include cresol, xylenol, diethyleneglycol diether,gamma-butyrolactone and tetramethylenesulfone. Alternatively, apolyamide-acid product may be recovered from the reaction mixture andadvanced to a polyimide by heating with a dehydrating agent such as amixture of acetic anhydride and beta picoline. Processes similar to theforegoing are described in U.S. Pats. No. 4,153,783; 4,736,015; and5,061,784.

A Pyridine Product such as a diaminopyridine may also be converted intoa polyurea oligomer or polymer by reaction with a polyisocyanate,representative examples of which include toluene diisocyanate; methylenebis(phenyl isocyanates); hexamethylene diisocycanates; phenylenediisocyanates. The reaction may be run in solution, such as bydissolving both reagents in a mixture of tetramethylene sulfone andchloroform with vigorous stirring at ambient temperature. The productcan be worked up by separation with water, or acetone and water, andthen dried in a vacuum oven. Processes similar to the foregoing aredescribed in U.S. Pat. No. 4,451,642 and Kumar, Macromolecules 17, 2463(1984). The polyurea forming reaction may also be run under interfacialconditions, such as by dissolving the diaminopyridine in an aqueousliquid, usually with an acid acceptor or a buffer. The polyisocyanate isdissolved in an organic liquid such as benzene, toluene or cyclohexane.The polymer product forms at the interface of the two phases uponvigourous stirring. Processes similar to the foregoing are described inU.S. Pat. No. 4,110,412 and Millich and Carraher, Interfacial Syntheses,Vol. 2, Dekker, New York, 1977. A diaminopyridine may also be convertedinto a polyurea by reaction with phosgene, such as in an interfacialprocess as described in U.S. Pat. No. 2,816,879.

A Pyridine Product such as a tetramino pyridine may be converted to apyridobisimidazole-2,6-diyl(2,5-dihydroxy-p-phenylene) polymer bypolymerizing a 2,5-dihydroxyterephthalic acid with thetrihydrochloride-monohydrate of tetraminopyridine in strongpolyphosphoric acid under slow heating above 100° C. up to about 180° C.under reduced pressure, followed by precipitation in water, as disclosedin U.S. Pat. No. 5,674,969 (which is incorporated in its entirety as apart hereof for all purposes); or by mixing the monomers at atemperature from about 50° C. to about 110° C., and then 145° C. to forman oligomer, and then reacting the oligomer at a temperature of about160° C. to about 250° C. as disclosed in U.S. Provisional ApplicationNo. 60/665,737, filed Mar. 28, 2005 (which is incorporated in itsentirety as a part hereof for all purposes), published as WO2006/104974. The pyridobisimidazole-2,6-diyl(2,5-dihydroxy-p-phenylene)polymer so produced may be, for example, apoly(1,4-(2,5-dihydroxy)phenylene-2,6-pyrido[2,3-d: 5,6-d′]bisimidazole)polymer, or apoly[(1,4-dihydrodiimidazo[4,5-b:4′,5′-e]pyridine-2,6-diyl)(2,5-dihydroxy-1,4-phenylene)]polymer. The pyridobisimidazole portionthereof may, however, be replaced by any or more of a benzobisimidazole,benzobisthiazole, benzobisoxazole, pyridobisthiazole and apyridobisoxazole; and the 2,5-dihydroxy-p-phenylene portion thereof maybe replaced by the derivative of one or more of isophthalic acid,terephthalic acid, 2,5-pyridine dicarboxylic acid, 2,6-naphthalenedicarboxylic acid, 4,4′-diphenyl dicarboxylic acid, 2,6-quinolinedicarboxylic acid, and 2,6-bis(4-carboxyphenyl)pyridobisimidazole.

EXAMPLES

The advantageous attributes and effects of the processes hereof may beseen in a series of examples (Examples 1˜11), as described below. Theembodiments of these processes on which the examples are based areillustrative only, and the selection of those embodiments to illustratethe invention does not indicate that conditions, arrangements,approaches, steps, techniques, configurations or reactants not describedin these examples are not suitable for practicing these processes, orthat subject matter not described in these examples is excluded from thescope of the appended claims and equivalents thereof.

Materials.

The following materials were used in the examples. All commercialreagents, such as glutaronitrile (99%) and 2-methylglutaronitrile (99%),were obtained from Aldrich and used as received unless otherwise noted.Palladium (10 weight percent on activated carbon) or platinum (5 weightpercent on activated carbon) slurry catalysts were obtained from Aldrichand used for all experiments unless otherwise noted. Anhydrous ammonia(99.99%) was obtained from Messer (GTS) and2,4-bis(dimethylamino)pentanedinitrile was prepared according toprocedures reported by Meerssche et al, J. Chem. Soc. Perkin Trans. II,1988, 1045-52.

Methods

The conversion and selectivity of this reaction are influenced by thecatalyst and conditions used. As used herein, the term “selectivity” fora product P denotes the molar fraction or molar percentage of P in thefinal product mix. As used herein, the term “conversion” denotes to howmuch reactant was used up as a fraction or percentage of the theoreticalamount. The conversion times the selectivity thus equals the maximum“yield” of P; the actual yield, also referred to as “net yield,” willnormally be somewhat less than this because of sample losses incurred inthe course of activities such as isolating, handling, drying, and thelike. As used herein, the term “purity” denotes what percentage of thein-hand, isolated sample is actually the specified substance.

¹H and ¹³C NMR spectra were recorded at 500 and 100 MHz (CCAS),respectively, unless otherwise specified. Percent conversion, based onthe mole fraction of reacted glutaronitrile (GN), and yield, based onthe mole fraction of 2,6-diaminopyridine (DAP) or2,6-diamino-3-methylpyridine (DAMP) produced in the reaction, weredetermined by ¹H NMR spectral integration and/or gas chromatography(HP5890 Series II equipped with FID detector) using internalstandards[2,6-Di-tert-butyl-4-methylphenol (BHT) andtriethyleneglycoldiethylether (EEE), respectively] unless otherwisespecified.

The meaning of abbreviations is as follows: “DAP” means2,6-diaminopyridine, “eq.” means equivalent “GN” means glutaronitrile,“h” means hour(s), “g” means gram(s), “mg” means milligrams, “mmol”means millimole(s), “MPa” means megapascal(s), “wt %” means weightpercentage), “psi” means pounds per square inch, “MHz” means megahertz,“NMR” means nuclear magnetic resonance spectroscopy, “Pd.C” meanspalladium on carbon catalyst, “Pt.C” means platinum on carbon catalystand “GC/MS” means gas chromatography/mass spectrometry.

Examples 1 through 9 demonstrate the preparation of 2,6-diaminopyridineby means of the reaction:

In Examples 1, 2, 3 and 4, the concentration of NH₃ is varied. InExamples 5, 6 and 7, the amount of catalyst is varied. In Example 8,different amounts of both catalyst and NH₃ are used. In Example 9, a Ptcatalyst is used instead of Pd.

Example 1

Glutaronitrile (3.0 g, 31.9 mmol, 1 eq.) was combined with Pd.C (3.39 g,3.19 mmol, 10 mol % of 10 wt % Pd on carbon) in a 400 mL Hastelloyshaker autoclave to which liquid NH₃ (1.0 g, 58.7 mmol, 1.8 eq.) wasadded. The mixture was heated at 200° C. for 45 h and maintained areaction pressure of approximately 90 psi (0.62 MPa). The mixture wascooled to ambient temperature and the excess NH₃ removed by N₂ purge.The crude mixture was suspended in 200 mL anhydrous methanol, thecatalyst was removed by gravity filtration, and the crude reactionmixture was concentrated in vacuo. Glutaronitrile conversion was >95% togive 2.43 mmol of 2,6-diaminopyridine in 7.6% net yield.

Example 2

Glutaronitrile (3.0 g, 31.9 mmol, 1 eq.) was combined with Pd.C (3.39 g,3.19 mmol, 10 mol % of 10 wt % Pd on carbon) in a 400 mL Hastelloyshaker autoclave to which liquid NH₃ (11.0 g, 0.65 mol, 20.2 eq.) wasadded. The mixture was heated at 200° C. for 45 h and maintained areaction pressure of approximately 800 psi (5.5 MPa). The mixture wascooled to ambient temperature and the excess NH₃ removed by N₂ purge.The crude mixture was suspended in 200 mL anhydrous methanol, thecatalyst was removed by gravity filtration, and the crude reactionmixture was concentrated in vacuo. Glutaronitrile conversion was >95% togive 2.07 mmol of 2,6-diaminopyridine in 6.5% net yield.

Example 3

Glutaronitrile (3.0 g, 31.9 mmol, 1 eq.) was combined with Pd.C (3.39 g,3.19 mmol, 10 mol % of 10 wt % Pd on carbon) in a 400 mL Hastelloyshaker autoclave to which liquid NH₃ (33.0 g, 1.94 mol, 60.7 eq.) wasadded. The mixture was heated at 200° C. for 45 h and maintained areaction pressure of approximately 1700 psi (11.7 MPa). The mixture wascooled to ambient temperature and the excess NH₃ removed by N₂ purge.The crude mixture was suspended in 200 mL anhydrous methanol, thecatalyst was removed by gravity filtration, and the crude reactionmixture was concentrated in vacuo. Glutaronitrile conversion was >95% togive 5.51 mmol of 2,6-diaminopyridine in 17.3% yield.

Example 4

Glutaronitrile (3.0 g, 31.9 mmol, 1 eq.) was combined with Pd.C (3.39 g,3.19 mmol, 10 mol % of 10 wt % Pd on carbon) in a 400 mL Hastelloyshaker autoclave to which liquid NH₃ (43.5 g, 2.55 mol, 80.1 eq.) wasadded. The mixture was heated at 200° C. for 45 h and maintained areaction pressure of approximately 2100 psi (14.5 MPa). The mixture wascooled to ambient temperature and the excess NH₃ removed by N₂ purge.The crude mixture was suspended in 200 mL anhydrous methanol, thecatalyst was removed by gravity filtration, and the crude reactionmixture was concentrated in vacuo. Glutaronitrile conversion was >95% togive 1.68 mmol of 2,6-diaminopyridine in 5.3% net yield.

Example 5

Glutaronitrile (3.0 g, 31.9 mmol, 1 eq.) was combined with Pd.C (0.34 g,0.32 mmol, 1 mol % of 10 wt % Pd on carbon) in a 400 mL Hastelloy shakerautoclave to which liquid NH₃ (33.0 g, 1.94 mol, 60.7 eq.) was added.The mixture was heated at 200° C. for 45 h and maintained a reactionpressure of approximately 1800 psi (12.4 MPa). The mixture was cooled toambient temperature and the excess NH₃ removed by N₂ purge. The crudemixture was suspended in 200 mL anhydrous methanol, the catalyst wasremoved by gravity filtration, and the crude reaction mixture wasconcentrated in vacuo. Glutaronitrile conversion was >95% to give 0.05mmol of 2,6-diaminopyridine in 0.2% net yield.

Example 6

Glutaronitrile (3.0 g, 31.9 mmol, 1 eq.) was combined with Pd.C (1.70 g,1.60 mmol, 5 mol % of 10 wt % Pd on carbon) in a 400 mL Hastelloy shakerautoclave to which liquid NH₃ (33.0 g, 1.94 mol, 60.7 eq.) was added.The mixture was heated at 200° C. for 45 h and maintained a reactionpressure of approximately 1800 psi (12.4 MPa). The mixture was cooled toambient temperature and the excess NH₃ removed by N₂ purge. The crudemixture was suspended in 200 mL anhydrous methanol, the catalyst wasremoved by gravity filtration, and the crude reaction mixture wasconcentrated in vacuo. Glutaronitrile conversion was >95% to give 4.86mmol of 2,6-diaminopyridine in 15.5% net yield.

Example 7

Glutaronitrile (3.0 g, 31.9 mmol, 1 eq.) was combined with Pd.C (6.79 g,6.38 mmol, 20 mol % of 10 wt % Pd on carbon) in a 400 mL Hastelloyshaker autoclave to which liquid NH₃ (33.0 g, 1.94 mol, 60.7 eq.) wasadded. The mixture was heated at 200° C. for 45 h and maintained areaction pressure of approximately 1800 psi (12.4 MPa). The mixture wascooled to ambient temperature and the excess NH₃ removed by N₂ purge.The crude mixture was suspended in 200 mL anhydrous methanol, thecatalyst was removed by gravity filtration, and the crude reactionmixture was concentrated in vacuo. Glutaronitrile conversion was >95% togive 4.466 mmol of 2,6-diaminopyridine in 14.6% net yield.

Example 8

Glutaronitrile (3.0 g, 31.9 mmol, 1 eq.) was combined with Pd.C (6.79 g,6.38 mmol, 20 mol % of 10 wt % Pd on carbon) in a 400 mL Hastelloyshaker autoclave to which liquid NH₃ (43.5 g, 2.55 mol, 80.1 eq.) wasadded. The mixture was heated at 200° C. for 45 h and maintained areaction pressure of approximately 2200 psi (15.2 MPa). The mixture wascooled to ambient temperature and the excess NH₃ removed by N; purge.The crude mixture was suspended in 200 mL anhydrous methanol, thecatalyst was removed by gravity filtration, and the crude reactionmixture was concentrated in vacuo. Glutaronitrile conversion was >95% togive 5.22 mmol of 2,6-diaminopyridine in 16.5% yield.

Example 9

Glutaronitrile (94 mg, 1.0 mmol, 1 eq.) was combined with Pt.C (390 mg,0.1 mmol, 10 mol % of 5 wt % Pt on carbon) in a 10 mL Hastelloy shakertube to which liquid NH₃ (1.0 g, 58.7 mmol, 59 eq.) was added. Themixture was heated at 200° C. for 45 h. The mixture was cooled toambient temperature and the excess NH₃ removed by N₂ purge. The crudemixture was suspended in 10 mL anhydrous methanol, the catalyst wasremoved by syringe filtration, and the crude reaction mixture wasconcentrated in vacuo. Glutaronitrile conversion was 97.2% to give 0.06mmol of 2,6-diaminopyridine in 4.8% net yield.

Example 10 demonstrates the preparation of 3-methylpyridine-2,6-diamineby means of the reaction:

Example 10

2-Methylglutaronitrile was combined with Pd.C (5 mol % of 10 wt % Pd oncarbon) in a 10 mL Hastelloy shaker autoclave to which liquid NH₃ wasadded. The mixture was heated at 200° C. for 45 h. The mixture wascooled to ambient temperature and the excess NH₃ removed by N₂ purge.The crude mixture was suspended in 10 mL anhydrous methanol, thecatalyst was removed by syringe filtration, and the crude reactionmixture was concentrated in vacuo. 2-Methylglutaronitrile conversion was100% to give 0.02 mmol of 3-methylpyridine-2,6-diamine in 2.3% netyield.

Example 11 demonstrates the preparation of a new compound by means ofthe reaction:

Example 11

2,4-bis(dimethylamino)pentanedinitrile (95 mg, 0.53 mmol, 1 eq.) wascombined with Pd.C (56 mg, 5.3×10⁻² mmol, 10 mol % of 10 wt % Pd oncarbon) and anhydrous NH₃ (1 g, 0.60 mol, 113.0 eq.) in a 10 mLHastelloy shaker. The crude mixture was suspended in 10 mL anhydrousmethanol, the catalyst was removed by syringe filtration, and the crudereaction mixture was concentrated in vacuo. 2,4-Bis(dimethylamino)pentanedinitrile conversion was >95%. The product,N³,N³,N⁵,N⁵-tetramethylpyridine-2,3,5,6-tetraamine (M⁺195), was detectedby GC/MS.

Features of certain of the processes of this invention are describedherein in the context of one or more specific embodiments that combinevarious such features together. The scope of the invention is not,however, limited by the description of only certain features within anyspecific embodiment, and the invention also includes (1) asubcombination of fewer than all of the features of any describedembodiment, which subcombination may be characterized by the absence ofthe features omitted to form the subcombination; (2) each of thefeatures, individually, included within the combination of any describedembodiment; and (3) other combinations of features formed by groupingonly selected features of two or more described embodiments, optionallytogether with other features as disclosed elsewhere herein.

In this specification, unless explicitly stated otherwise or indicatedto the contrary by the context of usage, where an embodiment of thesubject matter hereof is stated or described as comprising, including,containing, having, being composed of or being constituted by or ofcertain features or elements, one or more features or elements inaddition to those explicitly stated or described may be present in theembodiment. An alternative embodiment of the subject matter hereof,however, may be stated or described as consisting essentially of certainfeatures or elements, in which embodiment features or elements thatwould materially alter the principle of operation or the distinguishingcharacteristics of the embodiment are not present therein. A furtheralternative embodiment of the subject matter hereof may be stated ordescribed as consisting of certain features or elements, in whichembodiment, or in insubstantial variations thereof, only the features orelements specifically stated or described are present.

1. A process for the synthesis of a compound as described by thestructure of Formula (I)

comprising contacting a compound as described by the structure ofFormula (II)

with a chemical oxidant, and optionally also with a dehydrogenationcatalyst, in liquid ammonia neat, or in a mixture of liquid ammonia anda polar, aprotic solvent, to form a reaction mixture; and heating thereaction mixture to produce a Formula (I) compound; wherein R¹ and R²are each independently selected from (a) H; (b) a hydrocarbyl group; (c)NR³R⁴ wherein R³ and R⁴ are each independently selected from H and ahydrocarbyl group;

wherein R⁵ is a hydrocarbyl group; and (e) YR⁶ wherein Y is selectedfrom O and S and R⁶ is selected from H, a hydrocarbyl group, and

wherein R⁵ is a hydrocarbyl group.
 2. The process of claim 1 wherein oneor both of R¹ and R² is H.
 3. The process of claim 1 wherein one or bothof R¹ and R² is NH₂.
 4. The process of claim 1 wherein one or both of R¹and R² is N(CH₃)₂.
 5. The process of claim 1 wherein the reactionmixture comprises liquid ammonia neat.
 6. The process of claim 1 whereinthe reaction mixture comprises liquid ammonia and a polar, aproticsolvent.
 7. The process of claim 1 wherein the reaction mixturecomprises a chemical oxidant in the absence of a dehydrogenationcatalyst.
 8. The process of claim 1 wherein the reaction mixturecomprises a chemical oxidant and a dehydrogenation catalyst.
 9. Theprocess of claim 1 wherein the reaction mixture comprises a chemicaloxidant, and the chemical oxidant is selected from the group consistingof sulfur, sulfur dioxide, oxygen, selenium,2,3-dichloro-5,6-dicyano-p-benzoquinone,2,3,5,6-tetrachloro-p-benzoquinone, aluminum chloride, arsenic oxide,manganese dioxide, potassium ferricyanide, nitrobenzene, chlorine,bromine, and iodine.
 10. The process of claim 1 wherein the reactionmixture comprises a dehydrogenation catalyst, and the dehydrogenationcatalyst comprises a homogeneous catalyst.
 11. The process of claim 10wherein the homogeneous catalyst comprises at least one metal or metalsalt, wherein the at least one metal or metal salt is selected fromelements of Group VIII and salts of said elements.
 12. The process ofclaim 10 wherein the homogeneous catalyst is selected from the groupconsisting of ruthenium, rhodium, palladium, osmium, iridium, platinum;and salts thereof.
 13. The process of claim 1 wherein the reactionmixture comprises a dehydrogenation catalyst, and the dehydrogenationcatalyst comprises a heterogeneous catalyst.
 14. The process of claim 13wherein the heterogeneous catalyst comprises at least one metal or metalsalt and a support, wherein a metal or metal salt is selected fromelements of Groups IVA, VA, VIA, VIIA, VIII, IB and IIB of the periodictable, and salts of said elements.
 15. The process of claim 14 whereinthe support is selected from the group consisting alumina, titania,cobaltic oxide, zirconia, ceria, molybdenum oxide, tungsten oxide,silica, silicalite, titania, a zeolite or zeotype material having astructure made up of tetrahedra joined together through oxygen atoms toproduce an extended network with channels of molecular dimensions andhaving SiOH and/or AlOH groups on the external or internal surfaces,activated carbon, coke, and charcoal.
 16. The process of claim 6 whereinthe polar, aprotic solvent is selected from the group consisting of1,4-dioxane, tetrahydrofuran, acetone, acetonitrile, dimethylformamide,pyridine, and a mixture of 1,4-dioxane plus pyridine.
 17. The process ofclaim 1 further comprising a step of subjecting the Formula (I) compoundto a reaction to prepare therefrom a compound, oligomer or polymer. 18.The process of claim 17 wherein a polymer prepared comprises apyridobisimidazole-2,6-diyl(2,5-dihydroxy-p-phenylene) polymer, or apoly[(1,4-dihydrodiimidazo[4,5-b:4′,5′-e]pyridine-2,6-diyl)(2,5-dihydroxy-1,4-phenylene)]polymer.
 19. A compound as described bythe structure of Formula (III):